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A Preclinical Rodent Model of Radiation-induced Lung Injury for Medical Countermeasure Screening in Accordance With the FDA Animal Rule

Jackson, Isabel L.*; Xu, Puting; Hadley, Caroline; Katz, Barry P.; McGurk, Ross§; Down, Julian D.**; Vujaskovic, Zeljko

doi: 10.1097/HP.0b013e31826386ef
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The purpose of preclinical murine model development is to establish that the pathophysiological outcome of the rodent model of radiation-induced lung injury is sufficiently representative of the anticipated pulmonary response in the human population. This objective is based on concerns that the C57BL/6J strain may not be the most appropriate preclinical model of lethal radiation lung injury in humans. In this study, the authors assessed this issue by evaluating the relationship between morbidity (pulmonary function, histopathologic damage) and mortality among three strains of mice: C57BL/6J, CBA/J, and C57L/J. These different strains display variations in latency and phenotypic expression of radiation-induced lung damage. By comparing the response of each strain to the human pulmonary response, an appropriate animal model(s) of human radiation-induced pulmonary injury was established. Observations in the C57L/J and CBA/J murine models can be extrapolated to the human lung for evaluation of the mechanisms of action of radiation as well as future efficacy testing and approving agents that fall under the “Animal Rule” of the U.S. Food and Drug Administration (FDA) (21 CFR Parts 314 and 601).

*Division of Translational Radiation Sciences, Dept. of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD 21201; †Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710; ‡Department of Biostatistics, Indiana University School of Medicine, Indianapolis, IN 46202; §Medical Physics Graduate Program, Duke University Medical Center, Durham, NC 27710; **Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA.

The authors declare no conflicts of interest.

For correspondence contact: Zeljko Vujaskovic, Division of Translational Radiation Sciences, Professor, Dept. of Radiation Oncology, University of Maryland School of Medicine, Bressler Research Building 8-025, 655 W. Baltimore St., Baltimore, MD 21201 or email at: zvujaskovic@som.umaryland.edu.

(Manuscript accepted 6 June 2012)

© 2012 by the Health Physics Society